Disrupted-in-Schizophrenia-1 expression is regulated by β-site amyloid precursor protein cleaving enzyme-1–neuregulin cascade

• DOI: 10.1073/pnas.0909284107
• Publication Date: 2010-03-09T05:29:02Z
• Authors: Saurav Seshadri; Atsushi Kamiya; Yukako Yokota; Ingrid Prikulis; Shin-ichi Kano; Akiko Hayashi-Takagi; Amelia Stanco; Tae-Yeon Eom; Sarada Rao; Koko Ishizuka; Philip Wong; Carsten Korth; E. S. Anton; Akira Sawa
• Keywords: neuregulin 1; Neuregulin; DISC1; ERBB4; ErbB

Neuregulin-1 (NRG1) and Disrupted-in-Schizophrenia-1 (DISC1) are promising susceptibility factors for schizophrenia. Both multifunctional proteins with roles in a variety of neurodevelopmental processes, including progenitor cell proliferation, migration, differentiation. Here, we provide evidence linking these together single pathway, which is mediated by ErbB receptors PI3K/Akt. We show that signaling NRG1 NRG2, but not NRG3, increase expression an isoform DISC1 vitro. Receptors ErbB2 ErbB3, ErbB4, responsible transducing this effect, PI3K/Akt also required. In knockout mice, selectively reduced during neurodevelopment. Furthermore, similar decrease seen β-site amyloid precursor protein cleaving enzyme–1 (BACE1) NRG1/Akt reportedly impaired. contrast to neuronal was reported characterized, other types cells the brain has been addressed. Here demonstrate DISC1, like NRG proteins, expressed neurons, astrocytes, oligodendrocytes, microglia, radial progenitors. These findings may connect NRG1, ErbBs, Akt, common regulate neurodevelopment contribute